A very simple model system, the cellular slime mold, Dictyostelium discoideum, is being used to study mechanisms which control developmental gene activation during normal differentiation. Post-aggregation Dictyostelium cells transcribe an additional 26% of their genome, which is not expressed in earlier pre-aggregation-stage cells. Our previous studies have indicated that cell-cell interaction is a necessary prerequisite for the synthesis and stability of the late messenger RNAs. Following activation, the actual rate of transcription and the subsequent stability of many of the messenger RNAs transcribed off of this portion of the genome are further regulated by a cyclic AMP-mediated process. In these studies we have better defined the nature of the requirement for cell-cell interaction and have further attempted to develop conditions under which we can use transformation and in vitro mutagenesis to identify control sites involved in cAMP mediated regulation of developmental gene expression.